NIHR supported the CONSTRUCT trial to compare treatments for ulcerative colitis.
Published: 29 August 2019
Ulcerative colitis
Ulcerative colitis is a chronic debilitating disease that affects about 150,000 people in the UK. It is a long-term condition, where the colon (large bowel) and rectum become inflamed.
Small ulcers can develop on the colon’s lining, causing bleeding, recurring diarrhoea and abdominal pain. Acute severe ulcerative colitis (ASC) affects 25% of patients, and requires hospital admission and treatment with intravenous steroids.
About 40% of these patients do not respond to the standard steroid therapy and until 10 years ago colectomy was the only available treatment.
Comparing Ciclosporin and Infliximab
Ciclosporin and Infliximab are existing drugs which are used to treat people with ulcerative colitis, both are effective but infliximab is a newer drug and much more expensive than ciclosporin.
The CONSTRUCT (Comparison Of iNfliximab and ciclosporin in STeroid Resistant Ulcerative Colitis) trial aimed to test their relative clinical effectiveness, measured by quality of life and cost-effectiveness.
CONSTRUCT trial key features
• May 2010 - 2013
• 270 patients were recruited to the study
• 52 sites recruited at least one patient to the study
• Funded by the NIHR Health Technology Assessment programme
• Chief Investigator: Professor John Williams, Swansea University
• The results showed that ciclosporin is just as effective in treating ulcerative colitis and much cheaper for the NHS
Outcomes and findings
The study team conducted a pragmatic randomised trial using mixed quantitative and qualitative methods.
270 participants were recruited to the study from a ‘colitis cohort’ of patients admitted with ASC to 52 hospitals across Great Britain.
Infliximab
Participants randomised to infliximab received the drug through a drip over 2 hours, and then received a second and third dose at 2 and 6 weeks after the first dose.
Cyclosporin
Participants randomised to ciclosporin received the drug through a drip which continued for up to 7 days if successful, when it was switched to twice-daily oral tablets. After 12 weeks, treatment was at the discretion of the participant’s consultant.
For both treatments, participants were also able to receive steroid treatment from week 4 of the study at the discretion of the consultant and asked to discontinue by week 12 in participants who remained well.
The team assessed quality of life through patient-completed questionnaires at the start of the study, 3 and 6 months after treatment and then 6-monthly for 1 to 3 years.
The results showed both drugs are just as effective at treating ulcerative colitis and there was no significant difference in the quality-adjusted survival of either group of participants.
Interviews with participants revealed the substantial impact of ulcerative colitis on their quality of life, and the potential benefits from these medical treatments and from surgery.
Participants treated with infliximab generally spoke more positively about the treatment than those treated with ciclosporin.
Value to the NHS
Participants liked infliximab better than ciclosporin, but doctors were more equivocal. Nurses disliked the more resource-intensive drip-infusion requirements of ciclosporin.
In the primary analysis of the cost-effectiveness of the drugs, at 30 months, total health service costs for ciclosporin (£14,609) were significantly lower than for infliximab (£20,241).
By following participants over the next 10 years, through both questionnaires and routine data, the research team plans to extend its quantitative findings, especially on colectomies and other readmissions.
Key publications: